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Principal Investigator: Elena Vassilieva
Organization: EMORY UNIVERSITY
Fiscal Year: 2023
Award: $195,625
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is currently causing the
coronavirus disease (COVID-19) in pandemic proportion. According to John Hopkins university
data tracker, there
were 120,217,175 global cases and 2,660,456 deaths worldwide on March 15,
2021.
The disease ranges from asymptomatic to lethal, with the elderly patients most severely
affected. Finding a successful strategy to protect most vulnerable aged population is vital.
However, it is possible that protein-based vaccines will not be as effective in individuals over 65
years of age as in healthy younger adults.
There are also indications that RNA vaccines that are
currently used under emergency authorization elicit vaccine responses appear weaker in elderly
.
Protein-based vaccines are considered safe but they lack the ability to elicit Th1 type of responses
especially needed for protection in aged populations. Recently we developed a novel combination
adjuvant for use with a licensed influenza subunit vaccine in high-risk aged population and tested
it in an aged mouse model. The formulation combines an agonist of the stimulator of interferon
gene (STING) pathway 2,3’-cGAMP and saponin Quil-A. Activation of the STING pathway leads
to production of interferons and cytokines in target cells, and enhances development of the
immune response to vaccine antigens, while saponins stimulate both the Th1 immune response
and cytotoxic T lymphocyte production against protein antigens. By co-delivering these two
compounds, cGAMP and Quil-A, with the vaccine we combined their adjuvant potential and
improved the protective immunity of influenza vaccine in the aged mice more effectively than
either a 4x antigen dose or MF-59-like adjuvant, which are two current vaccination options for
persons over 65 years of age. We propose that this combination will also potentiate the protective
responses to a candidate SARS-CoV-2 vaccine and will test this in aged mice. We will test this
hypothesis using both sexes of aged mice. As saponins have been previously shown to increase
the duration of immune response we will also determine the persistence of neutralizing
antibodies in vaccinated animals. Although we do not anticipate reactogenicity of this formulation
based on our experience, we will also test if a novel and safer saponin Titerquil 1-0-5-5 can be
used instead of Quil-A. The results will be directly relevant for development of SARS-CoV-2
protein vaccines for high-risk aged populations. The combination adjuvant can be directly added
to existing vaccines.
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